Functional connectivity of the insular sub-regions in patients with disorders of consciousness

Poster No:

2328 

Submission Type:

Abstract Submission 

Authors:

Yihe Zhang1, Qiuyou Xie2, Yuting zhang1, Yuting He1, Taihan Chen1, Yanxuan Du1, Jingjing Yang1, Ruiwang Huang1

Institutions:

1School of Psychology, Key Laboratory of Brain, South China Normal University, Guangzhou, Guangdong, 2Department of rehabilitation medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong

First Author:

Yihe Zhang  
School of Psychology, Key Laboratory of Brain, South China Normal University
Guangzhou, Guangdong

Co-Author(s):

Qiuyou Xie  
Department of rehabilitation medicine, Zhujiang Hospital, Southern Medical University
Guangzhou, Guangdong
Yuting zhang  
School of Psychology, Key Laboratory of Brain, South China Normal University
Guangzhou, Guangdong
Yuting He  
School of Psychology, Key Laboratory of Brain, South China Normal University
Guangzhou, Guangdong
Taihan Chen  
School of Psychology, Key Laboratory of Brain, South China Normal University
Guangzhou, Guangdong
Yanxuan Du  
School of Psychology, Key Laboratory of Brain, South China Normal University
Guangzhou, Guangdong
Jingjing Yang  
School of Psychology, Key Laboratory of Brain, South China Normal University
Guangzhou, Guangdong
Ruiwang Huang  
School of Psychology, Key Laboratory of Brain, South China Normal University
Guangzhou, Guangdong

Introduction:

The insula and its sub-regions are important for maintenance of awareness and may be situated at an intermediate position along the brain's functional hierarchy1-3. Previous studies have shown that the insular dysfunction is related to disorders of consciousness (DoC), which is characterized by alterations in arousal and/or awareness4. The insula is a heterogeneous structure and can be divided into three sub-regions, the anterior insula (AI), middle insula (MI), and posterior insula (PI). Each of them has a distinct pattern of structural and functional connectivity5. Here, we attempted to measure the FC between each of the insular sub-regions and each voxel in the whole-brain and to detect the changed FC patterns in DoC patients.

Methods:

Participants: We recruited 22 DoC patients (DOCs) and 28 healthy controls (HCs) in the Guangzhou Liuhuaqiao Hospital (GLH). For each patient, the severity of the condition was assessed by the Coma Recovery Scale-Revised (CRS-R). This study was approved by the Institute Review Board (IRB) of the GLH, and the guardian of each patient gave written informed consent prior to the study.
Data acquisition: All the MRI data were acquired on a GE 3T MR scanner in the GLH. The rs-fMRI data were obtained using a single-shot GE-EPI sequence with the following parameters, TR = 2,000ms, TE = 26ms, flip angle = 90, FOV = 240mm×240mm, data matrix = 64×64, voxel size =3.75 × 3.75 × 4.20mm3 and 240 volumes. In addition, the high resolution brain structural images were acquired using a T1-weighted 3D FSPGR sequence (1mm isotropic voxel).
Data processing: The rs-fMRI data were preprocessed using SPM12 and CONN (ver 22.a)6. We removed the first 5 image volumes, performed slice-timing, corrected head-motion (criteria: 3 mm and 3°), normalized to the T1w images, resampled to a voxel size of (3mm)3 and smoothed with a 6 mm FWHM Gaussian kernel. The datasets for 2 patients were excluded because of their head motion exceeding the criteria.
Seed-based FC analysis: We defined the insular seed regions of interest (ROIs) according to the previous study7,8. Selected six spherical seeds with a radius of 6 mm were shown in Fig. 1 and mean coordinates for each cluster are provided in Table. 2. Individual FC maps of the bilateral AI, MI, and PI were generated by calculating Pearson's correlation coefficients between the mean time series of the ROIs and the time series of each voxel in the whole brain9. Then, a two-sample t-test was used to test the group difference in FC between the DOCs and HCs. The clusters were determined at the threshold of the voxel-level p < 0.001 and the cluster-level p < 0.001 (two-sided test). Age, sex and the mean FD were included as nuisance covariates in the comparisons.

Results:

Fig. 2 shows that the DoCs group had extensive FC abnormalities for different sub-regions of the insula. We found significant lower FC between the bilateral AI and AC/SMA, between left MI and right putamen, between right MI and SMA, between the left PI and AC/SMA, and between right PI and PostCG, than the controls. We also found significantly higher FC between the left AI and the SFG in the patients than the controls. The detailed information is listed in Table. 3.

Conclusions:

This study revealed that different insular sub-regions had different changes of FC patterns. The result indicated a graded functional heterogeneity in the insula: the AI is more involved in perceptual-motor translational functions such as motor control or attentional control, the MI is more related to integration of sensory-perceptual information, and the PI displays a low-level functions of sensorimotor behaviors10. The findings provide evidence for functional differentiation of insular sub-regions and cognitive-motor dissociation in disorders of consciousness.

Brain Stimulation:

Non-Invasive Stimulation Methods Other

Modeling and Analysis Methods:

Activation (eg. BOLD task-fMRI) 2

Novel Imaging Acquisition Methods:

BOLD fMRI 1

Keywords:

MRI

1|2Indicates the priority used for review
Supporting Image: fig1.png
Supporting Image: fig2.png
 

Provide references using author date format

1. Huang, Z. et al. Anterior insula regulates brain network transitions that gate conscious access. Cell Rep. 35, 109081 (2021).
2. Craig, A. D. B. How do you feel--now? The anterior insula and human awareness. Nat. Rev. Neurosci. 10, 59–70 (2009).
3. Bodien, Y. G., Chatelle, C. & Edlow, B. L. Functional Networks in Disorders of Consciousness. Semin. Neurol. 37, 485–502 (2017).
4. Zhang, L. et al. Functional Connectivity of Anterior Insula Predicts Recovery of Patients With Disorders of Consciousness. Front. Neurol. 9, 1024 (2018).
5. Chen, P. et al. Inflammation is associated with decreased functional connectivity of insula in unmedicated bipolar disorder. Brain. Behav. Immun. 89, 615–622 (2020).
6. Whitfield-Gabrieli, S. & Nieto-Castanon, A. Conn: a functional connectivity toolbox for correlated and anticorrelated brain networks. Brain Connect. 2, 125–141 (2012).
7. Chen, P. et al. Inflammation is associated with decreased functional connectivity of insula in unmedicated bipolar disorder. Brain. Behav. Immun. 89, 615–622 (2020).
8. B, D., Nb, P. & Ka, P. Three systems of insular functional connectivity identified with cluster analysis. Cereb. Cortex N. Y. N 1991 21, (2011).
9. Zhang, M. et al. Increased connectivity of insula sub-regions correlates with emotional dysregulation in patients with first-episode schizophrenia. Psychiatry Res. Neuroimaging 326, 111535 (2022).
10. Sohn, E. Decoding the neuroscience of consciousness. Nature 571, S2–S5 (2019).